Technical Abstract:
Genetic and antigenic diversity within H1 influenza A virus (IAV) subtypes circulating in swine is increasing. The need for cross-protective influenza vaccines in swine is necessary as the virus becomes more diverse. This study compared the humoral and cell-mediated immune response of modified live virus (MLV) vaccine, inactivated adjuvanted virus (INV) vaccine, and priming with wild-type virus (WTV) infection. Thirty-two influenza naive pigs were allocated to four groups consisting of a MLV, INV, WTV and sham-vaccinated (SHV) group. The MLV and WTV groups were given two intranasal doses of 10** TCID50/ml of an attenuated or wild-type A/Sw/MN/02011/08 delta-cluster virus (MN08), respectively. The INV group received 128 HA units in two intramuscular doses of UV-inactivated MN08 with adjuvant. Immune responses were evaluated with homologous MN08 and heterologous pandemic A/California/04/2009 H1N1 (CA09). Elevated numbers of interferon-gamma secreting cells to MN08 and CA09 were detected in the MLV and WTV groups compared to the INV and SHV groups. Hemagglutination inhibition (HI) and serum neutralizing (SN) anti-MN08 vaccine strain antibody responses detected in the MLV and WTV groups after first vaccination were not detected in the INV group. All vaccinated groups demonstrated similar HI and SN antibodies after the boost vaccination. Virus neutralizing (VN) anti-MN08 antibodies were only detected in the bronchoalveolar lavage fluid (BALF) of the MLV and WTV pigs post boost vaccination. Nasal wash (NW) anti-MN08 IgG and IgA antibodies in the upper respiratory tract were highest in the MLV pigs after two doses compared to the WTV and INV groups. No cross-reactive anti-CA09 heterologous challenge strain HI, SN, BALF VN or NW IgG or IgA antibodies were detected in any vaccinated group. The MLV, WTV and INV groups demonstrated similar anti-MN08 IgG and IgA BALF antibodies. However, MLV and WTV vaccinated pigs demonstrated a more robust anti-CA09 IgG and IgA BALF antibody response compared to the INV group. Collectively these data suggest the MLV vaccine induced a broader, locally acting adaptive (humoral and cellular) immune response against homologous vaccine and heterologous challenge strains.